Asymmetric Total Synthesis of (2R)-Hydroxynorneomajucin, a Norsesquiterpene from Illicium jiadifengpi

Abstract

We report the first total synthesis of (2R)-hydroxy­norneomajucin, a norsesquiterpene derived from the Illicium genus. This natural product displays neurotrophic properties. Small molecule neurotrophins have potential as therapeutics in neurodegenerative diseases. Key steps of our synthesis include a Tsuji–Trost reaction, a Pauson–Khand cyclization, and a Nagata hydrocyanation. A simple sequence of reductions and a Mukaiyama hydration introduce the A-ring substituents with the correct configurations. The overall synthesis was completed in 17 steps (longest linear sequence, LLS).

Selective preparative ‘oxidase phase’ in sesquiterpenoids: the radical approach

“…A regio- and stereoselective Mukaiyama hydration was the final step in the first total synthesis of (2 R )-hydroxynorneomajucin ( 151 ), reported by Rychnovsky's research team in 2022 (Scheme 15). 42 The latter sesquiterpene belongs to the seco-prezizaane family of terpenes derived from the Illicium genus of flowering plants. Among other interesting highly oxidized natural products of the same origin, many of which are presented in the context of this review, (2 R )-hydroxynorneomajucin holds a special position as its structure remained resistant to chemical synthesis although it had been known for more than ten years.…”